SHANGHAI and CHICAGO, June 1, 2024
/PRNewswire/ -- GenFleet Therapeutics, a clinical-stage
biotechnology company focusing on cutting-edge therapies in
oncology and immunology, today announced the phase II trial data of
KROCUS Study, fulzerasib (GFH925, KRAS G12C inhibitor) in
combination with cetuximab for first-line non-small cell lung
cancer (NSCLC) treatment,at the 2024 American Society of Clinical
Oncology (ASCO) annual meeting.
The preliminary result of the trial was accepted as a
late-breaking abstract and selected for oral presentation at the
clinical science symposium of lung cancer treatment, highlighting
the combination therapy's promising efficacy and its excellent
safety/tolerability profile. Notably, this marks the first time
that a KRAS G12C inhibitor is combined with an EGFR inhibitor as a
first-line NSCLC treatment with its data presented at a global
academic event.
The KROCUS Study, led by renowned lung cancer expert Dr.
Rafael Rosell, is a European
multi-center phase Ib/II study initiated in March 2023. As of April
19 this year, a total of 40 subjects were enrolled and 33 of
them received at least one available post-treatment tumor
assessment: the objective response rate (ORR) reached 81.8% and the
disease control rate (DCR) reached 100%. The post-treatment
evaluation revealed that most patients (27/33) exhibited tumor
response: one patient achieved complete response; the other two
achieved partial response with a shrinkage in their tumor size by
100%.
Additionally, the combination therapy demonstrated a favorable
safety/tolerability profile, with both treatment-related adverse
events (TRAEs) and TRAEs above grade 3 occurring at a lower rate
than those in the fulzerasib monotherapy study in second line and
above NSCLC. The data was presented by Dr. Vanesa Gregorc from Italy's Candiolo Cancer Institute,
Italy.
The new drug application for fulzerasib monotherapy in treating
advanced KRAS G12C-mutant NSCLC has been accepted and granted
priority review designation by China's National Medical Products
Administration (NMPA). Based on the data presented at 2023 ESMO
Asia, the registrational phase II study of GFH925 monotherapy for
NSCLC showed an ORR of 46.6% and a DCR of 90.5%; the median
progression-free survival (mPFS) was 8.3 months. In addition,
fulzerasib monotherapy received two breakthrough designations for
advanced G12C-mutant NSCLC and metastatic colorectal cancer (CRC)
patients.
"I am delighted that the preliminary data of this phase II trial
was selected for oral presentation at ASCO, an acknowledgement of
this innovative combination therapy's potential in treating NSCLC
patient in a of first-line setting. Currently, there are multiple
global trials exploring the combination of KRAS G12C and EGFR
inhibitors for later-line CRC. However, GenFleet is propelling the
validation of this synergistic mechanism further into first-line
treatment for NSCLC, the cancer type with the largest G12C-mutant
patient population. We eagerly anticipate the trial's continued
progress, aiming to offer more frontline options for patients
worldwide. "said Dr. Rafael Rosell,
the principal investigator of KROCUS study.
"The design of the KROCUS Study is based on deep research into
synergistic mechanisms, animal models validation, as well as
clinical data generated from the fulzerasib monotherapy in the
second-line setting. We are excited to see that the preliminary
data from our first-line combination study exceeding our
expectation. Furthermore, this chemo- and immuno-free combination
could potentially mitigate overlapped toxicities and delay drug
resistance, leaving space to allow later-line immunotherapy to
extend the patients' overall survival." stated by Yu Wang, M.D.,Ph.D., Chief Medical Officer of
GenFleet.
KROCUS: a Phase II study investigating the efficacy and
safety of fulzerasib (GFH925) in combination with cetuximab
in patients with previously untreated advanced KRAS G12C mutated
NSCLC
Presenter: Dr. Vanesa
Gregorc
Abstract No. : LBA8511
A total of 40 treatment naïve advanced KRAS G12C positive NSCLC
patients were treated with GFH925 in combination with cetuximab
(fulzerasib 600mg BID + cetuximab 500 mg/m2 Q2W) as of
April 19, 2024. Most patients (95%)
were diagnosed with stage IV disease and 13 (32.5%) patients with
brain metastases.
Efficacy: As of cutoff date, of the 33 patients who received at
least one post-treatment tumor assessment, investigator-assessed
ORR was 81.8% (95% CI: 64.5, 93.0) and DCR was 100% (95% CI: 89.4,
100); ORR among patients with brain metastasis was 70%. The
median duration of response (DoR) was not reached yet and 88% of
patients were still on treatment with a median follow-up of 5.1
months.
Safety: As of cutoff date, the combination therapy was well
tolerated. Treatment-related adverse events (TRAEs) occurred in
87.5% of subjects and the majority of the TRAEs were grade 1-2.
About 17.5% of subjects reported grade 3 TRAEs. There were no grade
4-5 TRAEs, and no TRAEs led to treatment discontinuation. No new
safety signals were identified compared with fulzerasib or
cetuximab as single agent.
About KROCUS Study and fulzerasib (GFH925)
The
multi-center study of fulzerasib in combination with cetuximab
started in scores of clinical research centers worldwide from
March 2023 and sets its objectives to
evaluate the safety/tolerance, efficacy and the pharmacokinetic
characteristics of the combination in advanced NSCLC patients
harboring KRAS G12C mutation.
Fulzerasib the first China-developed KRAS G12C inhibitor that has
its NDA submission accepted and granted with Priority Review
Designation by NMPA. Fulzerasib also received Breakthrough Therapy
Designations this year for treating advanced KRAS G12C-mutant NSCLC
patients that have received at least one systemic therapy and CRC
patients who have received at least two systemic therapies.
RAS protein family can be divided into KRAS, HRAS and NRAS
categories. KRAS mutations are detected in nearly 90% of pancreatic
cancer, 30-40% of colon cancer, and 15-20% lung cancer patients.
The occurrence of KRAS G12C mutation subset is more frequently
observed than those with ALK, ROS1, RET and TRK 1/2/3 mutations
combined. GFH925 is a novel, orally active, potent KRAS G12C
inhibitor designed to effectively target the GTP/GDP exchange, an
essential step in pathway activation, by modifying the cysteine
residue of KRAS G12C protein covalently and irreversibly.
Preclinical cysteine selectivity studies demonstrated high
selectivity of fulzerasib towards G12C. Subsequently, fulzerasib
effectively inhibits the downstream signal pathway to induce tumor
cells'apoptosis and cell cycle arrest.
View original
content:https://www.prnewswire.com/news-releases/genfleet-therapeutics-announces-efficacy--safety-result-from-phase-ii-trial-for-first-line-nsclc-treatment-in-krocus-study-fulzerasib-kras-g12c-inhibitor-in-combination-with-cetuximab-in-a-late-breaking-abstract-at-the-oral-p-302161182.html
SOURCE GenFleet Therapeutics